In 1959, Charles Edmund Ford and colleagues published “A Sex Chromosome Anomaly in a Case of Gonadal Dysgenesis (Turner’s Syndrome),” hereafter “A Sex Chromosome Anomaly,” in The Lancet. Turner syndrome is a chromosomal disorder that affects one in 2,000 female births and results in developmental issues such as short stature, infertility, and congenital heart disease. Prior to “A Sex Chromosome Anomaly,” researchers did not know the cause of Turner syndrome, but Ford and colleagues found that the cause is a sex chromosome irregularity. In the article, the team explains that they examined the cells of a person with Turner syndrome and determined that she had just one X chromosome instead of the typical two. Thus, they concluded that the cause of Turner syndrome is a missing X chromosome and called for a new classification of the condition. “A Sex Chromosome Anomaly” was one of the first papers to identify the cause of Turner syndrome, and it provided scientists with a better understanding of individuals with a nontypical sex chromosome pattern. 

Susumu Ohno studied chromosome structure and evolution during the twentieth century in the United States. Ohno was one of the first researchers to propose that the Barr body, a mass of genetic material within female mammalian cells, was a condensed X-chromosome. Ohno also developed a theory that gene duplication, when specific regions of a chromosome become multiplied, is a primary driver of evolution, with natural selection playing a secondary role. He theorized that gene duplication allows one copy of the original gene to remain and perform its normal function while a second copy of the gene can mutate and undergo natural selection, leading to diversification of life. Later in his career, Ohno composed music based on DNA sequences. As of 2025, researchers continue to debate Ohno’s theory of gene duplication. Through his research, Ohno introduced a new perspective on the driving forces of evolution, which advanced researchers’ understanding of chromosomal evolution and genetic diversity.

In 1961, Mary Lyon, a researcher who studied genetics, published “Gene Action in the X-chromosome of the Mouse (Mus Musculus L.),” hereafter “Gene Action in the X-chromosome,” in the journal Nature. Lyon’s paper focuses on the workings of female sex chromosomes, or X-chromosomes, and their implications for gene expression. A chromosome is a structure in a cell’s nucleus that contains the DNA, or genetic information, for each individual. In her paper, Lyon proposes her X-inactivation hypothesis, which states that one of the two X-chromosomes in mammalian female cells becomes inactive during early development, silencing its genetic activity. By describing X-chromosome inactivation, Lyon provided an explanation for the mosaic patterns observed in some female mammals, where different regions of their bodies exhibit distinct traits based on the genes carried by the particular X-chromosome that is active in that region. “Gene Action in the X-chromosome” provided evidence that X-chromosome inactivation occurs, laying the basis for understanding sex-linked traits, gene expression, and X-linked genetic diseases that impact thousands of people.

Mary Frances Lyon studied gene expression and developed the theory of X-chromosome inactivation, also called Lyonization, during the twentieth century in the United Kingdom. The Lyonization hypothesis proposes that, even though females have two X-chromosomes and males have only one, one X-chromosome in females is always randomly inactivated, which causes males and females to have the same level of X-chromosome gene expression. Prior to Lyon’s hypothesis, scientists understood that there must be a biological way to compensate for the difference in X-chromosomes in males and females, but they did not know the exact mechanism. To investigate the topic, Lyon studied coat color in mice, a trait influenced by genes on the X-chromosome. Her resulting hypothesis highlighted X-chromosome inactivation as a mechanism for controlling gene expression in females without altering their DNA sequence. Through her research, Lyon aided scientists in understanding X-linked disorders, which laid the foundation for the development of gene therapies designed to treat X-linked disorders that affect hundreds of thousands of people globally.