A new study has found that the X chromosome passed down to the child from the mother might be responsible for accelerated brain ageing, potentially increasing the risk of conditions like Alzheimer’s disease. Only females have two X chromosomes (XX) while males have one X and one Y (XY). Given the natural order, the X chromosome carries a significant amount of genetic material, and any mutation or variation here can have profound effects, especially as one X chromosome in females is randomly inactivated in each cell.

Though women tend to live longer than men and have lower rates of dementia, one exception is Alzheimer’s disease which affects them at higher rates. Even then, some studies suggest that females survive longer with Alzheimer’s than males do. The researchers set out to find the reason and believed that the sex chromosomes, X and Y, could help explain the differences.

“Skewing of the X chromosome is common among humans, and there are certainly women who are walking around with much higher or lower levels of maternal X chromosomes than others, just by chance,” said Dena Dubal, senior author of the paper.

“There has been little research on the potential consequences of this,” she added.

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‘The experiment’

To further explore the idea, the researchers experimented with female lab mice of different ages. In some cases, the paternal X chromosomes were silenced, leaving only the mother’s X active. These mice were compared with others that had a mix of maternal and paternal X’s switched on.

As per the findings, the young “Mom-X” mice were cognitively similar to young mice but the older ones showed steep cognitive decline. In the brains of these mice, the maternal X chromosome sped up biological ageing in the hippocampus – a brain area crucial for learning and memory.

“These findings raise the possibility that some women who express more of their mom’s X chromosome just by pure chance may have more cognitive impairment with aging or an increased risk for diseases like Alzheimer’s,” said Ms Dubal.

“Ultimately, it could also help us find constructive strategies for slowing brain aging in both sexes.”

Though the research was conducted on mice, the findings, if they translate to humans, could point to drivers of cognitive decline related to a particular sex and, eventually, help us fund ways to prevent or treat them.

After six decades of research, scientists have discovered the gene responsible for the orange fur seen in domestic cats. Two separate research teams found that the characteristic ginger, calico, and tortoiseshell colours in cats are due to a missing piece of DNA in a part of the cat’s genome that doesn’t make proteins. This breakthrough explains why some cats have their distinctive fiery fur.

“The sex-linked orange mutation in domestic cats causes variegated patches of reddish/yellow hair and is a defining signature of random X-inactivation in female tortoiseshell and calico cats. Unlike the situation for most coat colour genes, there is no apparent homolog for sex-linked orange in other mammals,” the authors of the study wrote.

“We show that the sex-linked orange is caused by a 5 kb deletion that leads to ectopic and melanocyte-specific expression of the Rho GTPase Activating Protein 36 (Arhgap36) gene. Single-cell RNA-seq studies from foetal cat skin reveal that red/yellow hair colour is caused by reduced expression of melanogenic genes that are normally activated by the melanocortin 1 receptor (Mc1r)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, but the Mc1r gene and its ability to stimulate cAMP accumulation are intact.”

“Instead, we show that increased expression of Arhgap36 in melanocytes leads to reduced levels of the PKA catalytic subunit (PKAC); thus, sex-linked orange is genetically and biochemically downstream of Mc1r. Our findings solve a comparative genomic conundrum, provide in vivo evidence for the ability of Arhgap36 to inhibit PKA, and reveal a molecular explanation for a charismatic colour pattern with a rich genetic history.”

“I am fully convinced this is the gene and am happy,” Carolyn Brown, a University of British Columbia geneticist who was not involved in either study, told Science. “It’s a question I’ve always wanted the answer to.”

As per a release, scientists have long been fascinated by tortoiseshell and calico cats: the offspring of a black cat and an orange cat. Multicoloured cats from such a cross are almost always female, suggesting the gene variant that makes fur orange or black is located on the X chromosome. The male offspring of such a cross are typically unicolor because they inherit just one parent’s X chromosome: We can guess, for instance, that Garfield’s mother is orange because he inherited his only X chromosome from her.