The Y chromosome is one of the two sex chromosomes in humans (the other is the X chromosome). The sex chromosomes form one of the 23 pairs of human chromosomes in each cell. The Y chromosome spans more than 59 million building blocks of DNA (base pairs) and represents almost 2 percent of the total DNA in cells. Geneticists have discovered that all human embryos start life as females, as do all embryos of mammals. About the 2nd month, the fetal tests elaborate enough androgens to offset the maternal estrogens and maleness develops.'Y' Chromosomes are also known as sex determination chromosomes.
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| [Chromosomes pairs in Female & Male] |
According to the results of a study published in Science, it is presumed that the loss of the Y chromosome in white blood cells can cause fibrosis in the heart resulting in impaired heart function and develop severe cardiovascular disease in men; however, the causal relationship with CVD and Y chromosome is still not clearly identified.
This study established a causal relationship when investigators from Uppsala University used the gene-editing tool, CRISPR, to generate mouse models with mLOY in their white blood cells. They found that mosaic loss of Y (mLOY) caused direct damage to the animals’ organs and that mice with mLOY had shorter survival than mice without mLOY.
“In the mouse models used in the study, the mouse 'Y ' chromosome was eliminated to mimic the human mLOY condition and had analyzed the direct consequences that this had,” Lars Forsberg, associate professor at the department of immunology, genetics, and pathology at Uppsala University, said in a statement. “Examination of mice with mLOY showed increased scarring of the heart, known as fibrosis. We see that mLOY causes fibrosis which leads to a decline in heart function,” Forsberg said. Investigators also were able to corroborate the causal effect in mice via epidemiological studies in humans. They found that mLOY was a new significant risk factor for death from CVD in men.
They found that men with mLOY in their blood at the start of the study displayed an approximately 30% increased risk of dying from heart failure and other types of CVD during the 11 years of follow-up. “ It has also been seen that men with a higher proportion of white blood cells with mLOY in the blood have a greater risk of dying from cardiovascular disease.
This observation is in line with the results from the mouse model and suggests that mLOY has a direct physiological effect also in humans,” Forsberg said. These studies were performed using data from the United Kingdom Biobank, a database with genomic and health information from half a million normally aging individuals aged 40 to 70 years at the start of the study.
The study described the mechanism by which mLOY in the blood causes disease in other organs and further identifies a possible treatment. Additionally, mLOY in a certain type of white blood cell in the heart of mice, called cardiac macrophages, stimulates a known signaling pathway that leads to increased fibrosis. When the research blocked the pathway, the pathological changes in the heart could be reversed.
“The link between mLOY and fibrosis is very interesting, especially given the new treatment strategies for heart failure, pulmonary fibrosis, and certain cancers that aim to counteract the onset of fibrosis. Men with mLOY could be a patient group that responds particularly well to such treatment,” Forsberg said.
